Philly Physicians Move Medicine Forward

FROM LEFT: Dr. Carl D. Regillo,
Dr. David L. Porter, and Dr.
Scott Schoifet are just three
of the physicians doing
groundbreaking medical
research in Philadelphia.

Cutting the quadriceps tendon
was standard procedure in knee
replacements, but Dr. Scott
Schoifet found a better way.

Vision loss often comes with
aging, but Dr. Carl D. Regillo is
using embryonic stem cells in
the hope of restoring sight.

Fine medical care has long been a hallmark of the City of Brotherly Love. Benjamin Franklin helped charter the Pennsylvania Hospital—the country’s oldest hospital—in 1752. The University of Pennsylvania established the nation’s first medical school in 1765. And the Wills Eye Institute opened in 1832 as America’s first eye hospital. Philadelphia was such a vibrant center of medical education and publishing in its early years that it was known as “the City of Medicine.”

That preeminence continues today, says David L. Porter, MD, the director of blood and marrow transplantation at Penn Medicine’s Abramson Cancer Center and a member of the headline-making team that developed a breakthrough approach to treating a form of leukemia just last year. “Philadelphia has a long and exciting history as a place for discovery and innovation,” he says. “It was here that the Philadelphia chromosome, the first description of a genetic abnormality that causes cancer, was identified, and that effort laid the groundwork for hundreds of scientists and physicians to work toward new therapies and cures for patients with cancers of all kinds.”

While breakthroughs in cancer treatment continue to garner national attention, there is cutting-edge work being done elsewhere in the city that is impacting lives right now—such as a knee replacement procedure that has patients leaving the hospital the same day—or will in the near future, like a stem cell therapy to minimize and possibly restore vision loss. Although only a few people become the public faces of these advancements, there is always a small army working behind the scenes, sometimes for decades, to turn treatment dreams into reality for the millions of people who desperately need help.

“The city is really an incubator for people to come together—from the many great research institutions, hospitals, and pharmaceutical and biotech companies that we are fortunate to have here—to solve problems in new, collaborative ways,” says Dr. Porter.

Joint Venture
Orthopedic surgeon Scott Schoifet, MD, of Virtua Health, the largest health provider in South Jersey, doesn’t expect thank-you letters. So he was surprised to get one from a patient who wrote, “This was a wonderful experience.” Says Dr. Schoifet, “A wonderful experience! I just cut them open and they’re telling me it’s a wonderful experience!” He has developed a technique for reducing the postoperative pain and recovery time from total knee replacement surgery. In the past, knee replacements usually meant significant pain and roughly six months of rehabilitation to restore strength and mobility. But Dr. Schoifet has performed some 4,000 total knee replacements, and afterward many patients have walked out of the hospital under their own power the same day.

The breakthrough? Not cutting the quadriceps, the tendon that attaches the knee to the large muscle group in the thigh. To replace the knee, the surgeon needs access to the whole joint, and previous approaches had cut the tendon to enable that. Afterward, the patient would need to rehabilitate not only the knee but also the tendon.

Dr. Schoifet knew that some surgeons were trying to develop a tendon-sparing surgery, so he observed a few procedures. “I watched and I thought, We can do this better.”

He developed new instruments for the surgery. Then, in late 2003, he operated on some patients without cutting the quadriceps tendon. “My very first patient I went to see was raising her leg in the air and bending without pain the day of surgery,” Dr. Schoifet reports. “Even though my early cases took twice as long, the patients got better twice as fast. There was no turning back from there.”

The new technique revolutionizes postoperative care, he says. “Ninety percent of our patients go home and not to a rehabilitation center after their surgery. While some patients are able to go home on the day of surgery, the majority spend, on average, one night in the Joint Replacement Institute recuperating and participating in physical therapy.”

Dr. Schoifet, who lives in Medford, New Jersey, with his wife and three sons, hopes his technique will be widely adopted. He acknowledges that it’s easier for a surgeon to cut the tendon, but the improved patient outcome and reduced hospital stay with his procedure should outweigh that consideration—and joint replacements are becoming more common as the population ages.

“When I was finishing my training, I loved joint replacement,” he says. “My fellow students wanted to work with younger patients. But I thought, There is going to be a lot of joint replacement needed, and it needs to be done well. I thought there was a lot of opportunity to try to improve it. And now I can get patients off the cane and back to sports and golf and exercise in six weeks.”

A Man With Vision
Carl D. Regillo, MD, chief of the Wills Eye Institute Retina Service, is a man with a mission. He’s taking on the number-one cause of severe vision loss in patients over 60: macular degeneration.

“Vision as a sense is highly valued,” Dr. Regillo says. “In general, people fear death as their number-one medical fear, and number two is losing their vision. We’re in a charged, anxious area when people have vision problems.”

Some degree of macular degeneration affects 11 million Americans, with many more to come. “It’s a huge public health risk as the elderly population expands,” he says.

There are two types of macular degeneration. Wet degeneration, which involves the growth of abnormal blood vessels in the eye, is now highly treatable if caught early. Dry degeneration is characterized by the slow, gradual drop-off of visual cells in the central retina or macula. In its advanced stages, patients lose their central vision.

“We still have a major frontier to tackle in terms of treating dry degeneration,” says Dr. Regillo. “It’s a hot area of research, and at Wills Eye we have a large clinical trial under way.”

A breakthrough treatment developed at Wills was announced late last year. A team led by Dr. Regillo injected a patient’s eye with between 50,000 and 200,000 retinal pigment epithelial cells, derived from a line of human embryonic stem cells. After the procedure, the patient recovered uneventfully.

“What we’re doing is a cell transplant,” Dr. Regillo explains. “We inject the cells under the retina, where they set up shop, grow, and proliferate. The great hope—and the great promise—is that they will allow cells to repopulate and rejuvenate. They should help support, nourish, and protect dying tissue to minimize vision loss. Replacing lost or damaged cells with functional and healthy cells could slow vision loss, and perhaps even reverse the effects of disease. And we see evidence that it’s working.”

Over the years, many of the special instruments and techniques that are commonplace in ophthalmology today were invented or developed at Wills Eye, including the intraocular lens implant, an artificial lens placed inside a cataract patient’s own clouded lens to restore vision. Wills researchers also invented one of the first vitrectomy machines, which are used to replace a clouded lens for clearer vision. In addition to macular degeneration, they are working on new ways to treat glaucoma, inflammatory eye disease, and eye cancers in children and adults.

“It’s hard to find a family who doesn’t have a member with macular degeneration,” says Dr. Regillo, who lives in Bryn Mawr. He admits that members of his own family have struggled with vision loss. “This is the most exciting and unique technique to come along in a long time.”

Cellular Zone
As the medical director of the team at Penn that developed a breakthrough T-cell immunotherapy for combating leukemia, “I’m the guy at the bedside,” says Dr. Porter—and he is grateful to be able to treat patients who are benefiting from the city’s continuing tradition of medical excellence.

T-cell immunotherapy involves reprogramming the body’s immune cells, enabling them to rapidly multiply and destroy specific cancerous cells. Last winter, Penn Medicine announced that two children with an aggressive form of childhood leukemia had experienced complete remission—that is, they showed no evidence of cancer in their bodies—after treatment with the new therapy. The news made headlines around the country.

“This therapy involves a technology that takes a patient’s own immune cells and genetically modifies them so that they now can recognize, and kill, their own leukemia cells,” says Dr. Porter, who cares for adults—some of whom have been his patients for more than 15 years—and works in tandem with pediatric oncologists involved in the trial. “For every cell we infuse into a patient, 1,000 to 93,000 cancer cells can be killed. The real breakthrough is the ability to genetically change somebody’s immune system. The modified cells have the potential to provide continuous protection against the cancer they target.”

One of the young patients, 7-year-old Emily Whitehead, experienced a dramatic recovery after a relapse following conventional treatment. Today she remains healthy and cancer-free. (Sadly, the other young girl in the study relapsed.) Two adult patients remain in remission more than two and a half years following their treatment.

“We’re hopeful that our efforts to treat patients with these personalized cellular therapies will reduce or even replace the need for bone marrow transplants, which carry a high mortality risk and require long hospitalizations,” says Carl H. June, MD, the director of translational research at the Abramson Cancer Center and the lead researcher on the T-cell project. (Dr. June does not see patients.) “In the long run,” he adds, “if the treatment is effective in these late-stage patients, we would like to explore using it up front, and perhaps arrive at a point where leukemia can be treated without chemotherapy.”

Dr. Porter says that immunotherapy eventually might be applied to different kinds of cancer. “I am extremely optimistic, though certainly cautious,” he says. “We are in the very early stages, but we have seen incredibly powerful anti-tumor responses.”

Because the therapy is so new and so experimental, it’s being tested only in patients who have few, if any, other treatment possibilities. Dr. Porter, who lives just outside Philadelphia with his wife and two young children, says the experience of seeing patients without hope get better has been highly emotional.

“Often this is the patient’s last chance to treat their cancer,” he explains. “You’re helping them through some of the most frightening, intense moments of their lives. It’s a very profound experience [for a physician].

“I have been treating a woman from Oregon. We recently had a long discussion about her staying in Philly or going home. So we worked out a program so she could see her family. Her daughter just sent me an e-mail with a picture attached of her and her grandson sitting in their family room with the message ‘Thanks for letting Grandma come home.’ [Working with cancer patients] has been the most rewarding and exciting experience of my career.”